5Treating Addictive Disorders

One of the most enduring myths about addiction is that treatment for these disorders is ineffective. This chapter provides a brief overview of the variety of types of treatments available, what is known about their effectiveness, and some questions that require further research. As previous chapters have described, addiction involves a complex interplay of biological, social, and individual factors. This interplay complicates treatment in much the same way that treatment for diabetes or hypertension is complicated by disease severity, the individual's motivation and ability to control diet or exercise levels, social support, and other factors.

O'Brien and McLellan (1996) reviewed and compared treatment literature for addictive disorders and three common health problems—hypertension, diabetes, and asthma. Treatment effectiveness for addiction was defined as a 50 percent reduction in drug taking after six months. The literature reviewed showed treatment for alcoholism to be successful for 40 percent to 70 percent of patients; success rates for cocaine addiction were 50 percent to 60 percent, opioids 50 percent to 80 percent, and nicotine 20 percent to 40 percent. Interestingly, review of studies relevant to diabetes, hypertension, and asthma revealed that high proportions of these patients did not follow their physicians' advice and did not adhere to diet and other behavioral components of their treatment. For example, among patients with insulin-dependent diabetes, less than 50 percent adhered to their medication regimen and less than 30 percent conformed to their diet and other self-care requirements. Less than 30 percent of patients with asthma or hypertension were found to take their medications as instructed. Noncompliance and other factors, according to the studies reviewed, resulted in 50

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5
Treating Addictive Disorders
One of the most enduring myths about addiction is that treatment for these disorders is ineffective. This chapter provides a brief overview of the variety of types of treatments available, what is known about their effectiveness, and some questions that require further research. As previous chapters have described, addiction involves a complex interplay of biological, social, and individual factors. This interplay complicates treatment in much the same way that treatment for diabetes or hypertension is complicated by disease severity, the individual's motivation and ability to control diet or exercise levels, social support, and other factors.
O'Brien and McLellan (1996) reviewed and compared treatment literature for addictive disorders and three common health problems—hypertension, diabetes, and asthma. Treatment effectiveness for addiction was defined as a 50 percent reduction in drug taking after six months. The literature reviewed showed treatment for alcoholism to be successful for 40 percent to 70 percent of patients; success rates for cocaine addiction were 50 percent to 60 percent, opioids 50 percent to 80 percent, and nicotine 20 percent to 40 percent. Interestingly, review of studies relevant to diabetes, hypertension, and asthma revealed that high proportions of these patients did not follow their physicians' advice and did not adhere to diet and other behavioral components of their treatment. For example, among patients with insulin-dependent diabetes, less than 50 percent adhered to their medication regimen and less than 30 percent conformed to their diet and other self-care requirements. Less than 30 percent of patients with asthma or hypertension were found to take their medications as instructed. Noncompliance and other factors, according to the studies reviewed, resulted in 50

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percent to 60 percent of hypertension and 60 to 80 percent of asthma patients needing to be retreated within a year.
The comparability of these data argue that addiction is similar to these three common medical illnesses in that they all can be treated successfully in many patients, but none can be cured and all four often require retreatment. Yet, there are important differences between addiction and these other illnesses in the perception of the public, insurance companies, and physicians. Few would argue that retreatment for diabetes, hypertension, or asthma indicates treatment failure, or that re-treatment should be withheld from or denied to these patients when they relapse and their symptoms reoccur. Yet such an argument is commonly made about addiction.
Similar to the treatment of many illnesses, addiction treatment involves three major stages—detoxification (or acute stabilization), rehabilitation, and follow-up care (McLellan et al., 1997). For all addictive disorders, the initial treatment goal is to help the person stop using alcohol, nicotine, cocaine, heroin, or other drugs and to begin to address the person's physiological, emotional, and motivational status. Detoxification can be accomplished in a variety of ways, depending on the drug(s) involved. For example, treatment of alcoholism usually requires complete abstinence from drinking, but treatment of heroin addiction often utilizes methadone as a substitute to achieve a gradual withdrawal and detoxification.
The rehabilitation phase of treatment continues the treatment components utilized initially, but can include additional components, such as education about the harmful effects of drugs and ways to avoid relapse, as well as behavioral or other types of therapy. Participation in support groups is also a common element of the rehabilitation phase. Follow-up or aftercare is the final phase of treatment for addiction. Aftercare varies considerably in terms of length and frequency of interventions, but prevention of relapse is the major goal of all aftercare strategies.
Relapse is the single most important target of addiction treatment. Data from clinical and outcomes research have shown that many types of treatment approaches are effective in reducing drug use and improving health, but that long-term abstinence is difficult to achieve (McLellan et al., 1995). McLellan and colleagues also found that the longer a person is in treatment, the more likely the treatment will be successful. A critical period seems to be the early stages of treatment, during which attrition is high. Additionally, the literature review provided a strong indication that treatment programs offering a greater variety of services (e.g., counseling, job training, housing assistance, and other services) targeted to an individual's specific problems tend to be most effective.
Despite the general effectiveness of addiction treatment, there is tremendous variation in the types of services offered, and considerable variation in the amount of information available regarding the effectiveness of the major types of treatment programs or any specific individual programs. In part, the variety reflects different approaches that have developed over time to address addiction

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to specific drugs (e.g., heroin vs. alcohol). In addition, not all strategies can be employed for specific addictions. For example, there are successful replacement pharmacotherapies available for heroin and nicotine addiction (methadone and nicotine gum or patches), but not for alcohol or cocaine. Often, however, treatment approaches are based on underlying assumptions and viewpoints regarding the causes of addiction, ranging from addiction as a disease to addiction as a moral failure.
The remainder of this chapter describes some of the various approaches taken, the relevant knowledge base, and the gaps in knowledge about treatment of alcohol and cocaine addiction first, followed by treatment for opioid addiction, and concludes with a description of some new advances in treatment for nicotine addiction. Some of the information in these sections overlaps, because there are certain elements common to all addiction treatment. However, it is important to keep in mind that success and failure in treatment involve both treatment factors (e.g., setting, length, intensity) and patient factors (e.g., severity of addiction, presence of other psychiatric and medical conditions, social support, education, and readiness for change). Although much is known about the general effectiveness of addiction treatment, the interaction of specific treatment factors with specific patient factors, often called patient-treatment matching, is an area of great interest in research.
TREATMENTS FOR ALCOHOL AND COCAINE ADDICTION
Treatment Setting
One of the variables in addiction treatment that is the subject of considerable research is the setting in which the treatment occurs. In general, these settings include inpatient versus outpatient settings, but outpatient settings also vary in their intensity and range from regular visits to a clinic to prolonged participation in day hospital programs. Treatment for alcoholism has been shaped in part by the legality of alcohol use, the predominance of Alcoholics Anonymous groups, and the availability of private insurance for many patients, leading to programs based on an initial hospital stay; whereas treatments for addiction to illegal drugs, such as heroin and cocaine, has developed largely with public funding, leading to a greater reliance on outpatient care and therapeutic communities. However, particularly for cocaine, these distinctions are blurring, which reflects the reality that many people addicted to one drug often are addicted to or abuse other drugs as well. This section emphasizes treatment approaches used for alcohol and cocaine addiction, because treatment of opioid addiction involves some significant differences discussed later in the chapter.

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TABLE 5.1 Duration of Addiction Treatment
Treatment Setting
Duration
Detoxification/stabilization (if necessary)
3–5 days
Inpatient, hospital-based programs
7–11 days
Residential, non-hospital programs
30–90 days
Therapeutic community programs
6 months–2 years
Outpatient, abstinence-oriented programs
30–120 days
Intensive outpatient
Begin at full or half days 5 times per week for one month, gradually decreasing
Aftercare (biweekly or monthly group meetings)
2 years
Maintenance treatments (e.g., methadone)
Years–lifetime
SOURCE: McLellan et al. (1997).
Decisions about treatment setting ideally take into account the overall status of the patient, and much work has been done to help guide such decisions. For example, the American Society of Addiction Medicine recently published a second edition of its Patient Placement Criteria (1997) which presents separate guidelines for adults and adolescents and defines five levels of service for each: early intervention, outpatient services, intensive outpatient/partial hospitalization services, residential/inpatient services, and medically managed intensive inpatient services. Table 5.1 summarizes the average length of treatment in various settings.
The American Psychiatric Association (1995) has published a set of clinical practice guidelines which address treatment issues for alcohol and other drug problems. Addiction severity measures have also been developed to help guide treatment decisions. For example, the Addiction Severity Index (ASI) was developed by McLellan and his colleagues (1980). The ASI assesses seven areas, including medical, employment and legal status, use of alcohol or other drugs, family-social interactions, and psychiatric status. The ASI has been shown to be reliable and valid for measuring severity of addiction and for tracking improvement during treatment.
Alcoholics Anonymous (AA), probably the best known approach to alcohol addiction, is a common component of aftercare for many patients, and is believed by many to be highly effective for individuals who are motivated to follow its 12-step program. However, AA considers itself a "fellowship" rather than a treatment program, and there are no objective studies of its effectiveness for individuals who voluntarily participate. The AA model has been applied to other drugs with the formation of Narcotics Anonymous (NA) groups for people with problems with drugs other than alcohol. The only two controlled studies of AA, which were published many years ago (Brandsma et al., 1980; Ditman and Crawford, 1966), found no evidence that AA improved outcomes for participants who were required to attend AA meetings by the criminal justice system. Some controlled studies, although not specifically focused on AA, have included

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AA as one of the treatment groups. For example, a study by Walsh and colleagues (1991) randomly assigned 227 alcohol-dependent workers identified through employee assistance programs to one of three groups—compulsory inpatient treatment, compulsory AA attendance, or a choice of treatment option. This study found that the compulsory inpatient treatment group scored better than the other two groups on 12 job-performance and 12 drinking and drug-taking measures over a two-year period. Of the remainder, the group who chose their treatment scored better than the group assigned to compulsory AA attendance, a result especially pronounced among the workers who had used cocaine in addition to alcohol.
The Minnesota model of inpatient treatment is used for most alcohol inpatient treatment in the United States, but it has been largely evaluated in uncontrolled studies, making it difficult to determine its effectiveness (Hester, 1994; IOM, 1989). The only controlled study of the Minnesota model found that it was slightly more effective than a more traditional therapy-based inpatient approach used in Finland; no comparisons were made to other American treatment approaches or to a no-treatment control group (Keso and Salaspuro, 1990). The Minnesota model program typically has a standardized length of stay (usually 28 days) consisting of detoxification, followed by educational lectures on such topics as the disease concept of addition, the effects of alcoholism (or drug abuse when applied to cocaine or other drugs) on families, relapse prevention techniques, and alternative coping mechanisms (Weiss, 1994). These programs often use self-disclosure forums similar to AA and NA and rely on group therapy and peer confrontation; recovering alcoholics often serve as counselors.
Chemical dependency treatment traditionally has been provided in an inpatient or residential program, although the term is increasingly used to refer to outpatient programs as well. In addition to the Minnesota Model, chemical dependency programs variously include 28-day, 12-step, or Hazelden-type treatment approaches, but these programs have traditionally been expensive and primarily for insured individuals (Gerstein, 1994). Chemical dependency programs were originally intended to treat alcohol problems, but they are now also used for patients who use illegal drugs. These programs usually provide intensive treatment, lasting 3 to 6 weeks, and patients help develop their own treatment plans patterned on the 12-step recovery model of AA and NA.
Therapeutic communities are considered another type of residential treatment, but include additional elements to address the multiple problems commonly associated with illegal drugs such as unemployment, criminal justice involvement, and other circumstances. Thus, these programs are important to consider for certain groups of individuals addicted to cocaine. Therapeutic communities provide treatment in a highly structured environment that typically uses no chemical agents except for medical or psychiatric reasons (Anglin and Hser, 1992). For individuals requiring extensive skills training and support in addition to drug treatment (e.g., homeless patients), therapeutic communities

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can be quite effective. These programs focus on the use of interpersonal relationships in an atmosphere of mutual self-help, and incorporate encounter group therapy, behavior modification, education classes, and residential job duties; later programs include jobs for clients who live in the facility and work in the outside community (De Leon, 1990; Sells, 1974). Treatment may be as short as 6 to 12 months, but traditional programs require at least 15 months in residence (Anglin and Hser, 1992). Phoenix House in New York City is a well-known example of a therapeutic community that treats all kinds of drug abuse.
National data from the Drug Abuse Reporting Project (DARP), collected from 1969 to 1973, and Treatment Outcomes Prospective Study (TOPS), collected between 1979 and 1981, studies indicated that therapeutic communities produced significant improvements in both immediate and long-term outcome (De Leon, 1984a,b). Drug use and criminal behavior decreased, while employment, school enrollment, and other pro-social behaviors increased (Anglin and Hser, 1992). A study at Phoenix House also showed increases in self-esteem and intelligence measures and decreases in personality disorders (De Leon, 1984b). Several studies indicated that clients who spent more time in therapeutic communities tended to improve more than those who spent less time (Anglin and Hser, 1992). Although high early drop-out rates were found to limit their effectiveness, individuals who managed to stay in the therapeutic community at least 12 months measurably benefited from the programs offered (De Leon, 1984b).
Certain important differences between treatment settings for alcohol or cocaine addiction need to be taken into account. For example, although studies have not demonstrated a clear advantage of initial inpatient treatment for alcoholism, in general there are greater medical complications from alcohol withdrawal than are observed from cocaine withdrawal (McLellan et al., 1997). Thus, inpatient treatment for alcoholism during the detoxification phase may be warranted for strictly medical reasons alone. Cocaine addiction can be initially treated taking an approach more focused on stabilization in an outpatient setting. One study comparing inpatient versus outpatient treatment for cocaine addiction found differences in completion of treatment between the groups, 89 percent completed inpatient versus 54 percent completed outpatient treatment, but a follow-up at 7 months revealed no differences between the groups in abstinence from cocaine (Alterman et al., 1994). This study however, excluded subjects with acute medical or psychiatric problems. It is known from many studies that drop-out rates are much higher among persons addicted to cocaine and, especially for those with significant co-occurring medical or psychiatric problems, inpatient treatment is likely to be more effective (Higgins et al., 1993; McLellan et al., 1997). Inpatient treatment may also be more useful for alcoholism if the patient has medical or psychiatric problems or is also abusing cocaine (Fleming and Barry, 1992), but may not be necessary in the absence of additional problems (Miller and Hester, 1986; Hayashida et al., 1989).

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Psychosocial or Behavioral Therapies
The American Psychiatric Association (APA) guidelines for the treatment of addictive disorders involving alcohol, cocaine, and opioids (1995) were developed based on intensive literature reviews and input from many clinical and research experts. These guidelines recommend psychosocial treatment as an essential element of treatment for addiction. As with treatment setting, however, the specific type of therapy needed varies and must take into account a variety of patient factors. The APA guidelines specifically endorse therapies that address cognitive and behavioral approaches, psychodynamic and interpersonal therapies, group and family therapies, and participation in self-help groups (e.g., AA).
A well-known literature review of psychosocial and other treatments for alcohol problems conducted by Hester in 1994 identified several approaches that have ''good evidence of effectiveness." These included behavioral marital therapy, brief interventions, community reinforcement approach, self-control training, social skills training, and stress management. These are described briefly below.
Behavioral marital therapy emphasizes improving communication and problem solving between spouses and increasing praise and other positive interactions.
Brief interventions, which may be provided by addiction specialists but are often provided by internists or other health care professionals in primary care settings, generally consist of the professional providing objective information about the patient's individual drinking problem, giving the patient the opportunity to take responsibility for changing his or her behavior, and one or two counseling sessions. These have been found in a number of studies to be as effective as longer-term inpatient and outpatient treatment (Bien et al., 1993; Hester, 1994; Kahan et al., 1995). It is important to note that these interventions often target at-risk individuals, do not necessarily result in total abstinence, and may vary in effectiveness in different populations (e.g., gender or different severity of drinking).
The Community Reinforcement Approach consists of a patient and therapist developing several strategies to address individual problems associated with alcohol abuse, such as taking Antabuse® (disulfiram), a drug that prevents drinking by causing an extremely unpleasant and potentially life-threatening physical reaction to alcohol; behavior-oriented marital counseling; and participation in healthy leisure time activities.
Self-control training teaches patients self-management skills that can be used to decrease or prevent alcohol consumption. These include setting goals, self-monitoring, rewarding oneself when goals are met, and learning new coping skills.

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Social skills training teaches patients how to form and maintain interpersonal relationships.
Stress management teaches individuals relaxation strategies and other ways to reduce tension and manage stress.
Although more research has been done examining psychosocial treatments for alcohol addiction, recent studies indicate differences between various therapies in cocaine treatment. For example, one study compared cocaine-addicted patients randomly assigned to either behavioral counseling, based on the community reinforcement model, or drug abuse counseling, based on a disease model (Higgins et al., 1993). The study found that 58 percent of the patients in the behavioral counseling group completed the 24-week, outpatient treatment, compared to only 11 percent in the drug abuse counseling group. Further, at 8 weeks, 68 percent of the behavioral counseling group maintained complete abstinence from cocaine, compared to only 11 percent in the other group; at 16 weeks, 42 percent of the behavioral and 5 percent of the drug abuse group had maintained abstinence. Even with pharmacotherapy for depression, psychosocial therapy may provide added benefits according to a study in which patients were randomly assigned to one of four conditions: relapse prevention therapy (a cognitive behavioral approach) and antidepressant medication (desipramine); clinical management and antidepressant; relapse prevention and placebo; or clinical management and placebo (Carroll et al., 1994a). Although neither the psychosocial therapy nor pharmacotherapy condition was associated with treatment retention or reduction in cocaine use, the more intensive relapse prevention approach was associated with higher abstinence in patients with more severe addiction and greater responses to treatment by depressed patients. In a follow-up study at one year, this research group found that the effect of psychotherapy increased over time, producing a delayed, but significantly improved outcome (Carroll et al., 1994b).
Treating accompanying psychiatric symptoms with pharmacotherapy and other means also has been shown to be useful in alcoholism treatment. A randomized controlled trial found depressed patients treated with the antidepressant, desipramine, remained abstinent from alcohol longer than controls (Mason et al., 1996). Another study with actively drinking, depressed outpatients found a marked reduction in alcohol consumption (McGrath et al., 1996). Similarly, treatment of anxiety with buspirone resulted in longer retention, reduced anxiety, and fewer drinking days in anxious alcoholics (Kranzler et al., 1994).

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Pharmacotherapy
As discussed previously, there are no replacement pharmacotherapies for alcoholism or cocaine addiction, but antidepressant, antianxiety, and other medication for accompanying psychiatric conditions are useful in the context of a comprehensive treatment program for addictive disorders involving alcohol and cocaine. A major advance in the treatment of alcoholism is the demonstrated efficacy of the opiate antagonist, naltrexone (ReVia™) in prolonging abstinence in alcoholism treatment. Naltrexone blocks opioid receptors in the brain reward system. When naltrexone was used in conjunction with behavioral therapy over a 3-month period, patients receiving the drug after discharge from inpatient treatment were half as likely to relapse compared to those receiving a placebo. Patients receiving naltrexone generally reported fewer drinking days, fewer drinks per session, and lowered craving scores (O'Malley et al., 1996). Naltrexone was approved by the Food and Drug Administration (FDA) for use in treating alcoholism in 1994, but it has not received enthusiastic support from many self-help groups, such as AA, many of whom believe that recovery from alcoholism is best accomplished by abstinence from all drugs.
In Europe two other drugs have been introduced for the treatment of alcohol addiction: acamprosate and gamma-hydroxybutyric acid. Studies have shown results with these medications similar to those seen with naltrexone (Gallimberti et al., 1992; Nalpas et al., 1990; Paille et al., 1995). For example, one randomized controlled trial found acamprosate resulted in higher early abstinence rates (67 percent at 60 days) compared to placebo (50 percent), longer abstinence duration (62 percent acamprosate, vs. 45 percent placebo), and lower drop-out rates (41 percent acamprosate, versus 60 percent placebo) (Sass et al., 1996). Both acamprosate and gamma-hydroxybutyric acid may mimic the actions of the neurotransmitter, gamma aminobutyric acid (GABA) in the brain, and additional clinical studies are underway in an effort to gain FDA approval for their use in the United States.
Disulfiram (Antabuse®) has been used for many years for the treatment of alcoholism. It causes nausea, vomiting, and other painful and potentially life-threatening side effects if alcohol is consumed, and must be taken daily, so its effectiveness depends on the patient's consistent compliance. Anton (1995) concluded that Disulfiram is effective when its use is closely monitored or where patients are highly motivated or very compliant. In recent years, innovative advanced behavior therapies have been used to sustain compliance.
Effective pharmacotherapy for cocaine addiction remains elusive and is a priority research issue, especially for the National Institute on Drug Abuse's (NIDA's) Medication Development Program (IOM, 1995a). Although pharmacotherapy for underlying psychiatric illness, such as the use of antidepressants to treat depression, seems to augment other therapeutic approaches in cocaine

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treatment, no medication has been found that specifically blocks craving for cocaine.
Matching Studies
Given the high number of variables that need to be considered in treatment of alcoholism or cocaine addiction, the research community has attempted to design studies to assess whether or not specific types of patients can be assigned to specific types of treatment to maximize the chances of success. This research, often referred to as patient-treatment matching, is aimed at providing an empirically derived knowledge base to improve patient placement criteria and treatment outcomes (McLellan and Alterman, 1991).
One of the largest of these studies, Project MATCH, was published in 1997 and involved an 8-year, multisite trial of alcoholism treatment that assessed three behavioral treatment conditions and 10 patient factors (NIAAA, 1997a). The treatment conditions were a 12-step facilitation therapy, cognitive-behavioral therapy (based on skill building to avoid relapse), and motivational enhancement therapy (based on using a patient's personal resources to effect change). The patient factors included alcoholism and psychiatric severity, cognitive and motivational, social support, and other types of measures. The results of this study were surprising and seemed to contradict clinical wisdom that the right "match" was necessary to optimize success. Of 11 hypothetical matches, only one was upheld by the data—patients with low psychiatric severity, treated as outpatients with 12-step facilitation therapy, did better than a similar group treated with cognitive-behavioral therapy. Interestingly, all participants in this study showed high levels of improvement, which were sustained over time, and one of the investigators has suggested that this improvement was the result of the overall high quality of treatment provided in the study across all treatment conditions (NIAAA, 1997b). If so, the study supports the concept that the overall quality of care across a range of treatment choices is crucial to the outcome of any given treatment.
It would be premature to conclude on the basis of the Project MATCH study that the concept of patient-treatment matching is flawed. One component not assessed in the study was pharmacotherapy, and future research will undoubtedly address more completely the effects of naltrexone in reducing craving for alcohol, as well as pharmacotherapies for co-occurring psychiatric conditions. There are already indications that such research will prove fruitful. For example, two recently published randomized trials studies suggest that treating depressed alcoholics with antidepressants and anxious alcoholics with antianxiety medications may be useful adjuncts to other treatment components (Kranzler et al., 1994; McGrath et al., 1996).
Multisite matching trials are underway to assess the effectiveness of different treatments for cocaine addiction, but individual studies offer support to the

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notion that attention to patient factors may be quite useful in determining treatment options for such patients. For example, the studies by Carroll and colleagues cited previously indicate that treating depression in cocaine-addicted patients with pharmacotherapy is associated with better outcomes and, thus, may be an appropriate match of multicomponent therapy with a specific patient characteristic (Carroll et al., 1994a,b).
TREATMENTS FOR OPIOID ADDICTION
Treatment for addiction to heroin and opioid drugs has many similarities to treatment for alcoholism or cocaine addiction. For example, the stages of treatment are the same, the same variety of types of treatment settings are used, and studies have examined the usefulness of a variety of treatment components. There is one clear difference and that is the availability of a "replacement" pharmacotherapy, methadone, for opioid addiction. Methadone substitutes for heroin but does not cause euphoria; thus, methadone can be used to help heroin-addicted individuals withdraw from heroin and avoid relapse. However, not all treatment strategies use methadone.
The four major types of publicly funded treatment programs for opioid addiction are detoxification, outpatient methadone maintenance, therapeutic communities, and outpatient drug-free programs (Anglin and Hser, 1992). Addiction research has tended to focus on the effectiveness of these publicly funded programs, especially for individuals addicted to heroin (see also Appendix E).
Another IOM committee has recommended replacing the term "detoxification" with "medically supervised withdrawal" to describe the acute or short-term (several days, several weeks, or a few months) administration of an approved long-acting opiate agonist drug to an individual patient, at a steadily reduced dose, on a schedule or rate such that the individual is able to continue to function with a tolerable level of discomfort and the use of short-acting opioids by the individual is discouraged (IOM, 1995b). However, research indicates that medically supervised withdrawal is relatively ineffective as a sole treatment. Many addicted individuals drop out of the programs as drug doses are progressively lowered (Lipton and Maranda, 1982; Maddux and Desmond, 1980), and the relapse rate is high; in one study 64 percent returned to daily opioid use during the first year, and 77 percent returned to some opioid use (Simpson and Sells, 1982). Many researchers and clinicians now consider a detoxification program to be an adjunct or precursor to other treatments rather than a treatment itself, since it can be used in emergency situations and enables addicted individuals to enter other treatment programs (McLellan et al., 1997).

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Methadone Maintenance Pharmacotherapy
The IOM committee also recommended replacing the term "methadone maintenance" with "maintenance pharmacotherapy," which it defined as ''sustained administration of an approved opiate agonist drug, at relatively stable doses, for the treatment of opiate addiction" (IOM, 1995b). Patients receive a stable dose, usually as outpatients, and are then usually required to receive counseling and rehabilitation services, undergo routine urine tests, and abstain from illegal opioid drugs. Maintenance pharmacotherapy is usually intended for patients who have been unable to succeed with drug-free forms of treatment (Anglin and Hser, 1992).
Maintenance pharmacotherapy has been extensively evaluated, and it has been found to significantly decrease opioid use and criminal behavior and improve general health while patients are in treatment, according to national data from DARP and TOPS, as well as other studies (Cooper et al., 1983; Senay, 1985; Tims and Ludford, 1984). After patients are taken off methadone, these improvements are still observable but lessen (Hser et al., 1988).
Researchers at UCLA who reviewed several studies reported that patients spent about 12 percent of their nonincarcerated time engaged in daily narcotics use while in methadone programs compared to about 70 percent when not in treatment, and the percentage of time that they abstained from all drugs increased from 12 percent to 26 percent (Anglin and Hser, 1992). Similarly, a study in New York City, Philadelphia, and Baltimore found that the average number of crime days per patient plunged from 307 days per year before treatment to 20 days per year after 6 months of treatment (Ball et al., 1987). In national experiments conducted after methadone programs closed, clients who did not enter other treatment programs were more likely to become readdicted to heroin, and their arrest and incarceration rates increased dramatically (Anglin and Hser, 1992).
New Pharmacotherapies for Opioid Addiction
Naltrexone (Revia™, formerly Trexan™), a selective opioid antagonist which was approved for the treatment of narcotic dependence in 1984, has been found to prevent relapse to opioid dependence in patients who are very highly motivated, such as parolees and health care professionals. This is the same drug that is also approved for use in treating alcoholism (see above). As an opioid antagonist, naltrexone works by preventing the euphoria and dependency-producing effects that would otherwise result from taking heroin or other opioid drugs.
As is generally the case for medical treatments of addiction, naltrexone has limited effectiveness when used alone and is significantly more effective in combination with behavior therapy or psychotherapy techniques (IOM, 1996).

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These findings are consistent with the view that addiction is best understood and treated using several approaches, in this case combining psychological and pharmacological therapies (Anton et al., 1995).
LAAM (levo-alpha-acetylmethadol), a synthetic opioid, has been introduced in the United States for the treatment of opioid addiction under the trade name Orlaam® (see Appendix G). LAAM reduces euphoria and suppresses withdrawal symptoms for up to 72 hours (IOM, 1995a). It works like methadone, but requires only three doses weekly instead of daily dosing, thereby increasing compliance among those treated.
Buprenorphine is a partial opioid agonist that in clinical trials was effective in maintenance therapy and helped keep patients in treatment. Buprenorphine produces less physiological dependence than methadone, but it causes some euphoria and therefore can be abused. An oral form of buprenorphine, that is combined with naloxone to reduce the potential for abuse, is currently being tested. Naloxone is not absorbed orally, but it would block the euphoric effects of buprenorphine if someone injected the combined medication.
SMOKING CESSATION PROGRAMS
Much of this chapter has examined treatment for opioid or cocaine addiction and alcoholism. It is useful, however, to consider briefly the application of various treatment strategies for nicotine addiction. The vast majority of adult smokers have tried to quit or would like to quit. Most smokers who try to quit do so without any formal cessation program, and many are successful. However, smoking cessation clinics and self-help groups have proliferated to help smokers unable to quit on their own. Early clinics offered lectures, pamphlets, medication, and physician counseling (DHHS, 1991). Clinics were offered in most major cities and many smaller communities in the 1970s and 1980s; these included clinics conducted by nonprofit groups such as the American Cancer Society and the Seventh Day Adventist Church, and commercial programs such as SmokEnders. Regardless of the type of program used, many were effective in helping smokers abstain initially, but long-term quit rates tended to be low, even following advice from physicians to quit smoking (Ockene et al., 1991, 1994; Law and Tang, 1995). Nevertheless, many investigators have argued that even the small long-term results achieved through physician and dentist intervention are worth the effort and may be up to 17 times more effective than doing nothing (Sachs, 1990). Many of the programs and self-help groups have now incorporated newer techniques and educational materials about relapse prevention, and are increasingly viewed as one component of a variety of approaches to treat nicotine addiction.
In 1996, the Agency for Health Care Policy and Research (AHCPR) of DHHS issued guidelines to help physicians encourage patients to quit smoking.

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The guidelines recommend that doctors ask every patient at every visit if they smoke; ask patients about their desire to quit smoking and reinforce such intentions, including helping set a quit date; motivate patients who are reluctant to quit; prescribe nicotine patches and nicotine gum; and refer patients for counseling when appropriate (DHHS, 1996).
Nicotine Chewing Gum
Nicotine chewing gum received FDA approval as an aid in smoking cessation in 1983 and was approved for over-the-counter use in 1996. The gum provides a slow release of nicotine, totaling 2 mg or 4 mg per piece (Haxby, 1995). Nicotine chewing gum has been thoroughly studied, and several meta-analyses clearly demonstrate its modest but statistically significant short-term effectiveness, especially when used in conjunction with intensive behavioral interventions (Cepeda-Benito, 1993; Haxby, 1995). Some studies indicate that nicotine gum is not effective when used with only brief advice and counseling in primary care settings; moreover, it is not effective in terms of long-term abstinence (Haxby, 1995); however, other studies suggest that nicotine gum can augment the effectiveness of brief physician interventions (Fiore et al., 1990; Ockene et al., 1991, 1994). There are several problems with the gum that may be responsible for its limited effectiveness. Perhaps most important, it has an unpleasant taste and 10 to 15 pieces must be chewed each day to provide the recommended nicotine replacement (Haxby, 1995). In addition, it requires a correct chewing technique and the avoidance of acidic beverages such as coffee, cola, and orange juice so that the nicotine is adequately absorbed (Haxby, 1995).
Nicotine Patches
Transdermal nicotine patches were approved by the FDA as smoking cessation aids in 1991 and 1992. Patches were first made available over-the-counter in 1996. Patches are easier to use than gum, because they deliver nicotine through the skin continuously over a 16- or 24-hour period. Despite skin reactions, which occur in 35 percent to 54 percent of patch users, compliance is considerably better than it is for the gum (Haxby, 1995). This greater compliance may account for the better success rates, which averaged twice as high as those using placebo patches (Fiore et al., 1992). Rates of smoking cessation varied greatly across studies, from a high of 77 percent 6 weeks after treatment to a low of only 18 percent three weeks after treatment (Fiore et al., 1992). Although success rates decrease after treatment is stopped, they are still considerably higher at 6 months than those for placebos, ranging from 22 percent to 42 percent compared to 2 percent to 28 percent for placebo patches (Fiore et al., 1992).

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Only recently has the combined use of nicotine patches and nicotine gum in overcoming nicotine addiction begun to be studied. By adding nicotine gum use, active patch users supplement their sustained nicotine release from the patch with repeated increases of plasma nicotine concentrations from the gum, helping to reduce withdrawal symptoms associated with abstinence from smoking (Benowitz, 1993; Fagerström, 1994; Fagerström et al., 1993). A preliminary study suggests that adding nicotine gum use to active patch use can increase abstinence rates among people who smoke 10 cigarettes or more a day—a statistically significant increase up to 6 months (Kornitzer et al., 1995). For those who used both the patch and gum, the abstinence rate was 27 percent after 6 months and 18 percent after 1 year (Kornitzer et al., 1995).
Studies similar to investigations with cocaine and alcohol are underway to assess the usefulness of antidepressant and other pharmacotherapies in addition to nicotine replacement. For example, the use of naltrexone is under investigation to reduce craving. Such studies have shown sufficient evidence of effectiveness of the antidepressant, bupropion hydrochloride (Wellbutrin®), for the FDA to approve its use, in May 1997, in conjunction with nicotine gum or patches, for treating nicotine addiction. All of the replacement and pharmacotherapeutic strategies for nicotine addiction are recommended to be used in conjunction with behavioral interventions, such as participation in support groups.
CONCLUSION
Extensive research has shown that treatment for addiction is as effective as treatments for other chronic, relapsing medical conditions. Advances in pharmacotherapy (Appendix G), basic science (Appendix F), and behavioral and social science research (Appendix H) have allowed the development of useful multimodal therapies for addiction that combine pharmacological and behavioral approaches. There are nevertheless significant differences in the treatment of specific addictions (e.g., cocaine versus opioid) and the challenge for future research is to identify ways to improve treatment success across a variety of conditions. Table 5.2 lists some of the key challenges to be addressed, requiring ongoing research in a variety of disciplines and a better base of interdisciplinary and health services and treatment outcomes research.

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TABLE 5.2 Some Future Challenges in Pharmacotherapy and Treatment Research
General Issues
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Development of better conceptual approaches to treatment evaluation
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Development of models of optimal pharmacological and behavioral interactions
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Evaluation of cue-dependent craving and clinical approaches to minimize the likelihood of relapse
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Development of objective measurements of craving in humans and development of animal models of craving
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Determination of the long-term (longer than 1 year) efficacy of brief intervention strategies and examination of factors predictive of success—for example, gender differences.
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Exploration of combination pharmacotherapy—for example, opioid antagonist and serotonin reuptake inhibitors in treating alcoholism relapse and craving. This approach appears reasonable in view of the multisite influence of ethanol in the regulation of the mesolimbic dopamine pathway by opioids, 5-HT and GABA. Further determination of subsets of alcoholics who might be more responsive to pharmacotherapy should be made
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Examination of the relationship between alcohol abuse and the abuse of cocaine, nicotine, opioids, and other drugs
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Examination of the behavioral consequences of the interaction of alcohol with other drugs of abuse and evaluation of the effect of medications for the treatment of codependence problems
Nicotine
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Evaluation of optimal combination of pharmacotherapy (with one drug or multiple drugs) and behavioral intervention for relapse prevention in humans
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Development of an acceptable nicotine antagonist for motivated smokers who have not succeeded with nicotine replacement therapy
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Further development of patient-treatment matching, especially treatments targeted at those subpopulations where smoking is most prevalent (e.g., smoking and alcohol, smoking and use of other psychoactive drugs, smoking in chronic psychotic patients)
Opioids
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Evaluation of optimal combination of pharmacotherapy (with one drug or multiple drugs) and behavioral intervention for relapse prevention in humans
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Demonstration of effectiveness of opioid tolerance and dependence blocking drugs in humans
Stimulants
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Evaluation of optimal combination of pharmacotherapy (with one drug or multiple drugs) and behavioral intervention for relapse prevention in humans
•
Successful demonstration of cocaine antagonist or partial agonist drugs in blocking cocaine effects in humans

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